Method and system for treatment of neurocardiogenic syncope

ABSTRACT

A method and apparatus for treating or preventing neurocardiogenic syncope is disclosed. Upon detection of bradycardia or a drop in blood pressure indicating the onset of syncope, electrostimulation pulses are delivered during the heart&#39;s refractory period. The pulses are non-excitatory but increase myocardial contractility and thereby increase cardiac output.

CROSS-REFERENCE TO RELATED APPLICATION(S)

This application is a continuation of U.S. patent application Ser. No.09/917,259, filed on Jul. 27, 2001, now issued as U.S. Pat. No.6,748,271, the specification of which is incorporated herein byreference.

FIELD OF THE INVENTION

This invention pertains to implantable medical devices and to methodsfor treating syncopal episodes.

BACKGROUND

Syncope, or fainting, is a transient loss of consciousness and posturaltone that may be due a number of etiologies, both cardiovascular andnon-cardiovascular. The most common pathophysiogical basis of syncope isan acute decrease in cerebral blood flow secondary to a decrease incardiac output, thereby causing cerebral hypoxia. Such a decrease incardiac output can be due to, for example, cardiac arrhythmias orcardiac outflow obstructions. Neurocardiogenic syncope is a relativelybenign condition in which dysfunction of the autonomic nervous systemcauses an inappropriate slowing of the heart (bradycardia) to result inhypotension. Classic neurogenic syncope (vasovagal syncope) occurs wheninappropriate reflex inhibition of the sympathetic nervous system andincreased parasympathetic activity causes both bradycardia andperipheral vasodilation. Vasovagal syncope may occur in otherwisehealthy individuals and in patients with a variety of underlyingdiseases. A number of factors may precipitate vasovagal syncope,including a hot or crowded environment, alcohol, extreme fatigue,hunger, chronic recumbency, prolonged standing, and emotional orstressful situations. Another type of neurocardiogenic syncope involvesfailure of the baroreceptor reflex to transiently increase the heartrate when an individual rises to an upright position, causing venouspooling in the lower extremities and decreased venous return to theright side of the heart.

Even if the cause of the syncope is benign, however, its consequencesmay not be. Falls during syncope can result in fractures, and episodesthat occur while driving can be extremely dangerous. Chronic andrecurring syncope can create a level of functional impairment similar tothat produced by other chronic debilitating disorders.

SUMMARY OF THE INVENTION

The present invention is a system and method for preventing and/ortreating syncope with cardiac electrostimulation delivered by animplantable medical device that increases cardiac output. The heart rateis monitored and, when bradycardia below a specified limit value isdetected that indicates the onset of a syncopal episode,electrostimulation pulses are delivered to a ventricle during itsrefractory period. Such electrostimulation pulses are non-excitatory butserve to increase the contractility of the ventricle. Stroke volume andcardiac output are thereby increased in order to prevent or lessen theseverity of the syncopal episode.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a system diagram of an exemplary cardiac rhythm managementdevice.

FIG. 2 is a flowchart illustrating an exemplary control scheme forimplementing the invention.

DETAILED DESCRIPTION

The present invention for treating neurocardiogenic syncope may beincorporated into various types of cardiac rhythm management deviceshaving means for sensing and electrostimulating the heart. As will bedescribed below, the invention may most conveniently be incorporatedinto a pacemaker.

1. System Description

Cardiac rhythm management devices are implantable devices that provideelectrical stimulation to selected chambers of the heart in order totreat disorders of cardiac rhythm and include pacemakers and implantablecardioverter/defibrillators. A pacemaker is a cardiac rhythm managementdevice that paces the heart with timed pacing pulses. The most commoncondition for which pacemakers are used is in the treatment ofbradycardia, where the ventricular rate is too slow. Atrio-ventricularconduction defects (i.e., AV block) that are permanent or intermittentand sick sinus syndrome represent the most common causes of bradycardiafor which permanent pacing may be indicated. If functioning properly,the pacemaker makes up for the heart's inability to pace itself at anappropriate rhythm in order to meet metabolic demand by enforcing aminimum heart rate. Pacing therapy may also be applied in order to treatcardiac rhythms that are too fast, termed anti-tachycardia pacing. (Asthe term is used herein, a pacemaker is any cardiac rhythm managementdevice with a pacing functionality, regardless of any other functions itmay perform such as the delivery cardioversion or defibrillation shocksto terminate atrial or ventricular fibrillation.)

Pacemakers are typically implanted subcutaneously on a patient's chestand have leads threaded intravenously into the heart to connect thedevice to electrodes used for sensing and pacing. A programmableelectronic controller causes the pacing pulses to be output in responseto lapsed time intervals and sensed electrical activity (i.e., intrinsicheart beats not as a result of a pacing pulse). Pacemakers senseintrinsic cardiac electrical activity by means of internal electrodesdisposed near the chamber to be sensed. A depolarization wave associatedwith an intrinsic contraction of the atria or ventricles that isdetected by the pacemaker is referred to as an atrial sense orventricular sense, respectively. In order to cause such a contraction inthe absence of an intrinsic beat, a pacing pulse (either an atrial paceor a ventricular pace) with energy above a certain pacing threshold isdelivered to the chamber.

FIG. 1 shows a system diagram of a microprocessor-based cardiac rhythmmanagement device suitable for delivering various cardiac rhythmmanagement therapies including treatment of neurocardiogenic syncope asdetailed below. The device is a pacemaker that is physically configuredwith sensing and pacing channels for both atria and both ventricles. Thecontroller 10 of the device is a microprocessor that communicates with amemory 12 via a bidirectional data bus. The memory 12 typicallycomprises a ROM (read-only memory) for program storage and a RAM(random-access memory) for data storage. The pacemaker has an atrialsensing and pacing channel comprising electrode 34, lead 33, sensingamplifiers 31, pulse generators 32, and atrial channel interface 30which communicates bidirectionally with microprocessor 10. The devicealso has a plurality of ventricular sensing and pacing/stimulationchannels for one or both ventricles, three of which are shown ascomprising electrodes 24 a-c, leads 23 a-c, sensing amplifiers 21 a-c,pulse generators 22 a-c, and ventricular channel interfaces 20 a-c. Inthis embodiment, a single electrode is used for sensing and pacing ineach channel, known as a unipolar lead. Other embodiments may employbipolar leads that include two electrodes for outputting a pacing pulseand/or sensing intrinsic activity. The channel interfaces 20 a-c and 30may include analog-to-digital converters for digitizing sensing signalinputs from the sensing amplifiers and registers which can be written toby the microprocessor in order to output pacing pulses, change thepacing pulse amplitude, and adjust the gain and threshold values for thesensing amplifiers. An exertion level sensor 330 (e.g., an accelerometeror a minute ventilation sensor) enables the controller to adapt thepacing rate in accordance with changes in the patient's physicalactivity. A telemetry interface 40 is also provided for communicatingwith an external programmer 500 that has an associated display 510.

Bradycardia pacing modes refer to pacing algorithms used to pace theatria and/or ventricles when the intrinsic ventricular rate isinadequate either due to AV conduction blocks or sinus node dysfunction.Such modes may either be single-chamber pacing, where either an atriumor a ventricle is paced, or dual-chamber pacing in which both an atriumand a ventricle are paced. Pacemakers can enforce a minimum heart rateeither asynchronously or synchronously. In asynchronous pacing, theheart is paced at a fixed rate irrespective of intrinsic cardiacactivity. There is thus a risk with asynchronous pacing that a pacingpulse will be delivered coincident with an intrinsic beat and during theheart's vulnerable period which may cause fibrillation. Most pacemakersfor treating bradycardia today are therefore programmed to operatesynchronously in a so-called demand mode where sensed cardiac eventsoccurring within a defined interval either trigger or inhibit a pacingpulse. Inhibited demand pacing modes utilize escape intervals to controlpacing in accordance with sensed intrinsic activity. In an inhibiteddemand mode, a pacing pulse is delivered to a heart chamber during acardiac cycle only after expiration of a defined escape interval duringwhich no intrinsic beat by the chamber is detected. If an intrinsic beatoccurs during this interval, the heart is thus allowed to “escape” frompacing by the pacemaker. Such an escape interval can be defined for eachpaced chamber. For example, a ventricular escape interval can be definedbetween ventricular events so as to be restarted with each ventricularsense or pace. The inverse of this escape interval is the minimum rateat which the pacemaker will allow the ventricles to beat, sometimesreferred to as the lower rate limit (LRL).

2. Cardiac Contractility Modulation

In accordance with the invention, when bradycardia below a specifiedthreshold that could otherwise cause syncope is detected by the device,one or more electrostimulatory pulses are delivered to the heart duringthe refractory period of one or more heartbeats. Such stimulation,referred to herein as cardiac contractility modulation (CCM), isnon-excitatory because it is delivered during the refractory period ofthe ventricle. (The refractory period of the ventricle in this caserefers to that portion of the ventricle to which is delivered theelectrostimulatory pulse being refractory.) It has been found that suchstimulation causes an increase in myocardial contractility, presumablyby increasing intracellular calcium concentration. The increase incontractility increases stroke volume so that more blood is pumped in asubsequent systolic contraction. The increased stroke volume counteractsthe bradycardia and thereby stabilizes cardiac output to either preventor shorten the duration of a syncopal episode. The invention may be adedicated implantable device or incorporated into an implantable cardiacrhythm management device such as a pacemaker, implantablecardioverter/defibrillator, or combination device.

Sensing of cardiac activity and delivery of CCM stimulatory pulses maybe accomplished using sensing/pacing channels otherwise used for pacingthe ventricles with a bradycardia pacing mode or using channelsdedicated for the purpose of delivering CCM pulses. In the device shownin FIG. 1, for example, any of the ventricular sensing/pacing channelsmay be used for delivering CCM stimulation pulses. FIG. 2 illustrates abasic control scheme for carrying out the method as would be implementedby programming the microprocessor 10. In the illustrated scheme, severaloptional steps are described that may or may not be implemented invarious embodiments. At step S1, the ventricular rate is continuouslymonitored by receiving ventricular senses representing intrinsicventricular depolarizations from one of the ventricular sensingchannels. To derive the ventricular rate VR, the interval betweensuccessive ventricular senses is measured and compared to a maximumlimit value in order to detect bradycardia as shown at step S2, wherethe inverse of the interval corresponding to the ventricular rate VR iscompared with a bradycardia limit value VR_(min). Bradycardia isdetected if VR<VR_(min), and delivery of CCM stimulation pulses is theninitiated at step S4 using one of the ventricular stimulation channels.The stimulation pulses are delivered during the refractory period of theventricle by timing a pulse to occur within a refractory intervalfollowing a ventricular sense or a ventricular pace if the device isalso operating in a bradycardia pacing mode. The device then returns tothe monitoring of the ventricular rate at step S1, and delivery of CCMpulses is terminated at step S3 if the ventricular rate VR equals orexceeds the limit value VR_(min). Optionally, the limit value VR_(min)may be increased to a hysteresis value VR_(min) at step S4 so that CCMpulse delivery is maintained until the heart rate rises above anincreased bradycardia limit value. In that case, the bradycardia limitvalue is returned to a non-hysteresis value at step S3 when CCM pulsedelivery is terminated. In another option, if the device is alsooperating in a bradycardia pacing mode, the lower rate limit may beincreased upon detection of bradycardia as shown at step S5. The heartis then paced at a faster rate simultaneously with the application ofcardiac contractility modulation.

Modifications may be made to the method so that one or more additionalcriteria are employed to confirm that a syncopal episode is taking placebefore CCM stimulatory pulses are delivered. One such modification isshown at step S1 where the measured intervals between ventricular sensesare moving average filtered in order to derive the ventricular rate VR.The moving average filter smooths the ventricular rate so thatbradycardia is not detected when long intervals occur solely due to thevariability of the instantaneous rate. Another optional modification isto measure the blood pressure as shown at step S2 and deliver CCMstimulatory pulses only if it is below a specified limit value. Theblood pressure measurement may be used instead of a sensed heart ratedecrease or may be used to confirm the rate decrease before initiatingtherapy. One way of measuring blood pressure in a cardiac rhythmmanagement device is to use an accelerometer, such as the exertion levelsensor 330, as described in U.S. Pat. No. 6,026,324, issued to Carlsonand hereby incorporated by reference. In a further refinement, themagnitude and/or duration of the CCM pulses can be increased as themeasured blood pressure decreases in order to maximize the effectivenessof the therapy.

Cardiac contractility modulation may also be applied to multiple sitesin order to distribute the effects of the stimulation pulses. Becausethis type of non-excitatory stimulation also increases local oxygenconsumption, distributing the stimulation over a plurality of sitesserves to help prevent potentially deleterious effects at thestimulation sites. Accordingly, at step S5 the ventricular stimulationchannels can be alternated with each stimulatory pulse so that thepulses are alternately delivered to electrodes 24 a-c.

Although the invention has been described in conjunction with theforegoing specific embodiment, many alternatives, variations, andmodifications will be apparent to those of ordinary skill in the art.Such alternatives, variations, and modifications are intended to fallwithin the scope of the following appended claims.

1. A method for operating a cardiac rhythm management device,comprising: sensing ventricular depolarizations and generatingventricular sense signals in accordance therewith; deriving aventricular rate as a function of a plurality of time intervals betweensuccessive ventricular senses; detecting a ventricular bradycardia whenthe derived ventricular rate is below a specified bradycardia limitvalue; initiating delivery of one or more electrostimulation pulses tothe ventricle while the ventricle is refractory when ventricularbradycardia is detected from the derived ventricular rate to therebyincrease the contractility of the ventricle, wherein suchelectrostimulation pulses are timed to occur within a refractoryinterval following a ventricular sense or pace; pacing the ventricleupon expiration of an escape interval without receipt of a ventricularsense, the inverse of the escape interval being the lower rate limit;and, increasing the lower rate limit when bradycardia is detected. 2.The method of claim 1 further comprising delivering theelectrostimulation pulse within the specified refractory time intervalafter each ventricular sense when bradycardia is detected.
 3. The methodof claim 1 further comprising terminating delivery of electrostimulationpulses when the ventricular rate equals or exceeds the bradycardia limitvalue.
 4. The method of claim 3 further comprising increasing thebradycardia limit value to a hysteresis value when delivery of theelectrostimulation pulses is begun and returning the bradycardia limitvalue to its previous non-hysteresis value when delivery of theelectrostimulation pulses is terminated.
 5. The method of claim 1further comprising alternating the delivery of the electrostimulationpulses between different stimulation sites of the ventricle.
 6. Themethod of claim 1 further comprising measuring a blood pressure anddelivering the electrostimulation pulses only when the measured bloodpressure is below a specified minimum value.
 7. The method of claim 6wherein the blood pressure is measured with an accelerometer.
 8. Themethod of claim 6 further comprising adjusting the magnitude of thestimulation pulses in accordance with the measured blood pressure. 9.The method of claim 6 further comprising adjusting the duration of thestimulation pulses in accordance with the measured blood pressure.
 10. Acardiac rhythm management device, comprising: a sensing amplifier forsensing ventricular depolarizations through a sensing channel andgenerating ventricular sense signals in accordance therewith; a pulsegenerator for delivering electrostimulation pulses to a ventriclethrough a stimulation channel; a controller for controlling the deliveryof stimulation pulses to the ventricle; wherein the controller isprogrammed to derive a ventricular rate as a function of a plurality oftime intervals between successive ventricular senses, detect aventricular bradycardia when the derived ventricular rate is below aspecified bradycardia limit value, and initiate delivery of one or morestimulation pulses while the ventricle is refractory when ventricularbradycardia is detected from the derived ventricular rate to therebyincrease the contractility of the ventricle, wherein suchelectrostimulation pulses are timed to occur within a refractoryinterval following a ventricular sense or pace; and, wherein thecontroller is configured to pace the ventricle upon expiration of anescape interval without receipt of a ventricular sense, the inverse ofthe escape interval being the lower rate limit, and to increase thelower rate limit when bradycardia is detected.
 11. The device of claim10 wherein the controller is programmed to deliver theelectrostimulation pulse within the specified refractory time intervalafter each ventricular sense when bradycardia is detected.
 12. Thedevice of claim 10 wherein the controller is programmed to terminatedelivery of electrostimulation pulses when the ventricular rate equalsor exceeds the bradycardia limit value.
 13. The device of claim 12further comprising specified hysteresis and non-hysteresis values forthe bradycardia limit value and wherein the controller is programmed toincrease the bradycardia limit value the hysteresis value when deliveryof electrostimulation pulses is begun and return the bradycardia limitvalue to the non-hysteresis value when delivery of electrostimulationpulses is terminated.
 14. The device of claim 10 further comprising aplurality of stimulation channels and wherein the controller isprogrammed to alternate the delivery of electrostimulation pulsesbetween different stimulation channels.
 15. The device of claim 10further comprising means for measuring blood pressure and wherein thecontroller is programmed to measure a blood pressure and deliver anelectrostimulation pulse only when the measured blood pressure is belowa specified minimum value.
 16. The device of claim 15 wherein the bloodpressure measuring means is an accelerometer.
 17. The device of claim 15wherein the controller is programmed to adjust the magnitude of thestimulation pulses in accordance with the measured blood pressure. 18.The device of claim 15 wherein the controller is programmed to adjustthe duration of the stimulation pulses in accordance with the measuredblood pressure.